CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications
Regulatory T cells are critical for maintaining immune tolerance. Recent studies have confirmed their therapeutic suppressive potential to modulate immune responses in organ transplant and autoimmune diseases. However, the unknown and nonspecific antigen recognition of polyclonal Tregs has impaired...
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Format: | Article |
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MDPI AG
2022-01-01
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Series: | Biomedicines |
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Online Access: | https://www.mdpi.com/2227-9059/10/2/287 |
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author | Motahareh Arjomandnejad Acadia L. Kopec Allison M. Keeler |
author_facet | Motahareh Arjomandnejad Acadia L. Kopec Allison M. Keeler |
author_sort | Motahareh Arjomandnejad |
collection | DOAJ |
description | Regulatory T cells are critical for maintaining immune tolerance. Recent studies have confirmed their therapeutic suppressive potential to modulate immune responses in organ transplant and autoimmune diseases. However, the unknown and nonspecific antigen recognition of polyclonal Tregs has impaired their therapeutic potency in initial clinical findings. To address this limitation, antigen specificity can be conferred to Tregs by engineering the expression of transgenic T-cell receptor (TCR) or chimeric antigen receptor (CAR). In contrast to TCR Tregs, CAR Tregs are major histocompatibility complex (MHC) independent and less dependent on interleukin-2 (IL-2). Furthermore, CAR Tregs maintain Treg phenotype and function, home to the target tissue and show enhanced suppressive efficacy compared to polyclonal Tregs. Additional development of engineered CAR Tregs is needed to increase Tregs’ suppressive function and stability, prevent CAR Treg exhaustion, and assess their safety profile. Further understanding of Tregs therapeutic potential will be necessary before moving to broader clinical applications. Here, we summarize recent studies utilizing CAR Tregs in modulating immune responses in autoimmune diseases, transplantation, and gene therapy and future clinical applications. |
first_indexed | 2024-03-09T22:33:00Z |
format | Article |
id | doaj.art-866573c17b8e4b23938c0829a2932558 |
institution | Directory Open Access Journal |
issn | 2227-9059 |
language | English |
last_indexed | 2024-03-09T22:33:00Z |
publishDate | 2022-01-01 |
publisher | MDPI AG |
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series | Biomedicines |
spelling | doaj.art-866573c17b8e4b23938c0829a29325582023-11-23T18:53:16ZengMDPI AGBiomedicines2227-90592022-01-0110228710.3390/biomedicines10020287CAR-T Regulatory (CAR-Treg) Cells: Engineering and ApplicationsMotahareh Arjomandnejad0Acadia L. Kopec1Allison M. Keeler2Horae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA 01655, USAHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA 01655, USAHorae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA 01655, USARegulatory T cells are critical for maintaining immune tolerance. Recent studies have confirmed their therapeutic suppressive potential to modulate immune responses in organ transplant and autoimmune diseases. However, the unknown and nonspecific antigen recognition of polyclonal Tregs has impaired their therapeutic potency in initial clinical findings. To address this limitation, antigen specificity can be conferred to Tregs by engineering the expression of transgenic T-cell receptor (TCR) or chimeric antigen receptor (CAR). In contrast to TCR Tregs, CAR Tregs are major histocompatibility complex (MHC) independent and less dependent on interleukin-2 (IL-2). Furthermore, CAR Tregs maintain Treg phenotype and function, home to the target tissue and show enhanced suppressive efficacy compared to polyclonal Tregs. Additional development of engineered CAR Tregs is needed to increase Tregs’ suppressive function and stability, prevent CAR Treg exhaustion, and assess their safety profile. Further understanding of Tregs therapeutic potential will be necessary before moving to broader clinical applications. Here, we summarize recent studies utilizing CAR Tregs in modulating immune responses in autoimmune diseases, transplantation, and gene therapy and future clinical applications.https://www.mdpi.com/2227-9059/10/2/287CAR Tregautoimmune diseasetransplantationgene therapyengineered Tregs |
spellingShingle | Motahareh Arjomandnejad Acadia L. Kopec Allison M. Keeler CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications Biomedicines CAR Treg autoimmune disease transplantation gene therapy engineered Tregs |
title | CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications |
title_full | CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications |
title_fullStr | CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications |
title_full_unstemmed | CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications |
title_short | CAR-T Regulatory (CAR-Treg) Cells: Engineering and Applications |
title_sort | car t regulatory car treg cells engineering and applications |
topic | CAR Treg autoimmune disease transplantation gene therapy engineered Tregs |
url | https://www.mdpi.com/2227-9059/10/2/287 |
work_keys_str_mv | AT motahareharjomandnejad cartregulatorycartregcellsengineeringandapplications AT acadialkopec cartregulatorycartregcellsengineeringandapplications AT allisonmkeeler cartregulatorycartregcellsengineeringandapplications |